Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy

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英文篇名：Phosphorylated TDP-43 Staging of Primary Age-Related Tauopathy 作者：Xiaoling ; Zhang ; Bing ; Sun ; Xing ; Wang ; Hui ; Lu ; Fangjie ; Shao ; Annemieke ; J.M.Rozemuller ; Huazheng ; Liang ; Chong ; Liu ; Jiadong ; Chen ; Manli ; Huang ; Keqing ; Zhu 英文作者：Xiaoling Zhang;Bing Sun;Xing Wang;Hui Lu;Fangjie Shao;Annemieke J.M.Rozemuller;Huazheng Liang;Chong Liu;Jiadong Chen;Manli Huang;Keqing Zhu;China Brain Bank and Department of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Department of Neurobiology, Zhejiang University School of Medicine;Department of Pathology, Zhejiang University School of Medicine;Department of Pathology, Amsterdam Neuroscience, VU University Medical Center;Brain Structure and Function Group, Neuroscience Research Australia;Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine; 英文关键词：TDP-43;;Primary age-related tauopathy;;Alzheimer's disease;;Neuro?brillary tangle;;Hippocampus 中文刊名：ZSJK 英文刊名：神经科学通报(英文版) 机构：China Brain Bank and Department of Neurology in Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of Zhejiang Province, Department of Neurobiology, Zhejiang University School of Medicine;Department of Pathology, Zhejiang University School of Medicine;Department of Pathology, Amsterdam Neuroscience, VU University Medical Center;Brain Structure and Function Group, Neuroscience Research Australia;Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine; 出版日期：2019-04-02 出版单位：Neuroscience Bulletin 年：2019 期：v.35 基金：supported by the National Science Foundation China (91632109 to JHZ, KQZ and HJH);; the Zhejiang Provincial Natural Science Foundation (LY16H090013 to KQZ);; the Zhejiang Medical and Health Science and Technology Plan Project (WKJ20132-009 to KQZ) 语种：英文; 页：ZSJK201902002 页数：10 CN：02 ISSN：31-1975/R 分类号：11-20

摘要

Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa TAR DNA-binding protein(pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART,Alzheimer's disease(AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages[ 0 and B IV, and a Thal phase of 0(no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus,stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.
        Primary age-related tauopathy(PART) is characterized by tau neurofibrillary tangles(NFTs) in the absence of amyloid plaque pathology. In the present study,we analyzed the distribution patterns of phosphorylated43-kDa TAR DNA-binding protein(pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART,Alzheimer's disease(AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages[ 0 and B IV, and a Thal phase of 0(no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus,stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.

引文

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